tbuckley/cabot-search huggingface dataset:
Addendum: Phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus
Authors: Joana Isidro, Vítor Borges, Miguel Pinto, Daniel Sobral, João Dourado Santos, Alexandra Nunes, Verónica Mixão, Rita Ferreira, Daniela Santos, Silvia Duarte, Luís Vieira, Maria José Borrego, Sofia Núncio, Isabel Lopes de Carvalho, Ana Pelerito, Rita Cordeiro, João Paulo Gomes
Journal: Nature Medicine (2022)

On 10 June 2022, a new nomenclature system for the monkeypox virus (MPXV) clades and lineages was proposed by Happi et al. 1 that defined the Clade 1 (former Congo Basin) and Clades 2 and 3 (both comprising the former West African clade).Our study, published online in Nature Medicine on 24 June 2022, relied on this nomenclature.Later, on 12 August 2022, the World Health Organization, together with a group of global experts, revised and agreed on the new naming convention for MPXV clades in which the previously proposed Clades 1, 2 and 3 are now designated Clades I, IIa and IIb, respectively 2 .The initial proposal by Happi et al. was subsequently updated 1 as well as the final corresponding publication 3 .
The Heterogeneity in the Landscape of Gene Dominance in Maize is Accompanied by Unique Chromatin Environments
Authors: Liangwei Yin, Gen Xu, Jinliang Yang, Meixia Zhao
Journal: Molecular Biology and Evolution (2022)

Subgenome dominance after whole-genome duplication (WGD) has been observed in many plant species. However, the degree to which the chromatin environment affects this bias has not been explored. Here, we compared the dominant subgenome (maize1) and the recessive subgenome (maize2) with respect to patterns of sequence substitutions, genes expression, transposable element accumulation, small interfering RNAs, DNA methylation, histone modifications, and accessible chromatin regions (ACRs). Our data show that the degree of bias between subgenomes for all the measured variables does not vary significantly when both of the WGD genes are located in pericentromeric regions. Our data further indicate that the location of maize1 genes in chromosomal arms is pivotal for maize1 to maintain its dominance, but location has a less effect on maize2 homoeologs. In addition to homoeologous genes, we compared ACRs, which often harbor cis-regulatory elements, between the two subgenomes and demonstrate that maize1 ACRs have a higher level of chromatin accessibility, a lower level of sequence substitution, and are enriched in chromosomal arms. Furthermore, we find that a loss of maize1 ACRs near their nearby genes is associated with a reduction in purifying selection and expression of maize1 genes relative to their maize2 homoeologs. Taken together, our data suggest that chromatin environment and cis-regulatory elements are important determinants shaping the divergence and evolution of duplicated genes.
After Metformin — Next Steps for Type 2 Diabetes with Low Cardiovascular Risk
Authors: Lars Rydén, Eberhard Standl
Journal: New England Journal of Medicine (2022)

In two articles in this issue of the Journal, the members of the GRADE Study Research Group1,2 report the findings of the Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness (GRADE) Study, which involved participants who had type 2 diabetes without established cardiovascular complications. These articles have been awaited with great anticipation. Most advances related to cardiovascular benefit in the treatment of type 2 diabetes have been derived from cardiovascular outcome trials involving participants with previous cardiovascular disease, and these advances have been related to secondary prevention. On the basis of those trials, the availability of two new . . .
IL-1RA Antibodies in Myocarditis after SARS-CoV-2 Vaccination
Authors: Lorenz Thurner, Christoph Kessel, Natalie Fadle, Evi Regitz, Franziska Seidel, Ingrid Kindermann, Stefan Lohse, Igor Kos, Carsten Tschöpe, Parastoo Kheiroddin, Daniel Kiblboeck, Marie-Christin Hoffmann, Birgit Bette, Gabi Carbon, Onur Cetin, Klaus-Dieter Preuss, Konstantinos Christofyllakis, Joerg T Bittenbring, Thomas Pickardt, Yvan Fischer, Holger Thiele, Stephan Baldus, Karl Stangl, Stephan Steiner, Frank Gietzen, Sebastian Kerber, Thomas Deneke, Stefanie Jellinghaus, Axel Linke, Karim Ibrahim, Ulrich Grabmaier, Steffen Massberg, Christian Thilo, Simon Greulich, Meinrad Gawaz, Ertan Mayatepek, Lars Meyer-Dobkowitz, Michael Kindermann, Einat Birk, Merav Birk, Mitja Lainscak, Dirk Foell, Philipp M Lepper, Robert Bals, Marcin Krawczyk, Dror Mevorach, Tal Hasin, Andre Keren, Michael Kabesch, Hashim Abdul-Khaliq, Sigrun Smola, Moritz Bewarder, Bernhard Thurner, Michael Böhm, Jochen Pfeifer, Karin Klingel
Journal: New England Journal of Medicine (2022)
Glycemia Reduction in Type 2 Diabetes — Microvascular and Cardiovascular Outcomes
Authors: David M Nathan, John M Lachin, Ionut Bebu, Henry B Burch, John B Buse, Andrea L Cherrington, Stephen P Fortmann, Jennifer B Green, Steven E Kahn, M Sue Kirkman, Heidi Krause-Steinrauf, Mary E Larkin, Lawrence S Phillips, Rodica Pop-Busui, Michael Steffes, Margaret Tiktin, Mark Tripputi, Deborah J Wexler, Naji Younes
Journal: New England Journal of Medicine (2022)

Data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to microvascular and cardiovascular disease outcomes in persons with type 2 diabetes.
Glycemia Reduction in Type 2 Diabetes — Glycemic Outcomes
Authors: David M Nathan, John M Lachin, Ashok Balasubramanyam, Henry B Burch, John B Buse, Nicole M Butera, Robert M Cohen, Jill P Crandall, Steven E Kahn, Heidi Krause-Steinrauf, Mary E Larkin, Neda Rasouli, Margaret Tiktin, Deborah J Wexler, Naji Younes
Journal: New England Journal of Medicine (2022)

The comparative effectiveness of glucose-lowering medications for use with metformin to maintain target glycated hemoglobin levels in persons with type 2 diabetes is uncertain.
Not just a gut feeling: a deep exploration of functional bacterial metabolites that can modulate host health
Authors: Andrew Gold, Jiangjiang Zhu
Journal: Gut Microbes (2022)

Bacteria have been known to reside in the human gut for roughly two centuries, but their modulatory effects on host health status are still not fully characterized. The gut microbiota is known to interact with dietary components and nutrients, producing functional metabolites that may alter host metabolic processes. The majority of thoroughly researched and understood gut microbial metabolites fall into two categories: short-chain fatty acids (SCFAs) and bacterial derivatives of dietary tryptophan. Despite the heavy emphasis on these metabolites, other metabolites stemming from microbial origin have significant impacts on host health and disease states. In this narrative review, we summarize eight recent studies elucidating novel bacterial metabolites, detailing the process by which these metabolites are identified, their actions within specific categories of human health, and how diet may impact production of these metabolites. With similar future mechanistic research, a more complete picture of bacterial impact on host metabolism may be constructed.
Viral proteases activate the CARD8 inflammasome in the human cardiovascular system
Authors: Rhea Nadkarni, Wern Cui Chu, Cheryl Q.E. Lee, Yasir Mohamud, Lynn Yap, Gee Ann Toh, Sheryl Beh, Radiance Lim, Yiyun Michelle Fan, Yizhuo Lyanne Zhang, Kim Robinson, Karl Tryggvason, Honglin Luo, Franklin Zhong, Lena Ho
Journal: The Journal of Experimental Medicine (2022)

Nucleotide-binding oligomerization domain (NBD), leucine-rich repeat (LRR) containing protein family (NLRs) are intracellular pattern recognition receptors that mediate innate immunity against infections. The endothelium is the first line of defense against blood-borne pathogens, but it is unclear which NLRs control endothelial cell (EC) intrinsic immunity. Here, we demonstrate that human ECs simultaneously activate NLRP1 and CARD8 inflammasomes in response to DPP8/9 inhibitor Val-boro-Pro (VbP). Enterovirus Coxsackie virus B3 (CVB3)-the most common cause of viral myocarditis-predominantly activates CARD8 in ECs in a manner that requires viral 2A and 3C protease cleavage at CARD8 p.G38 and proteasome function. Genetic deletion of CARD8 in ECs and human embryonic stem cell-derived cardiomyocytes (HCMs) attenuates CVB3-induced pyroptosis, inflammation, and viral propagation. Furthermore, using a stratified endothelial-cardiomyocyte co-culture system, we demonstrate that deleting CARD8 in ECs reduces CVB3 infection of the underlying cardiomyocytes. Our study uncovers the unique role of CARD8 inflammasome in endothelium-intrinsic anti-viral immunity.
Monitoring the Progression of a Calcifying Uterine Leiomyoma
Authors: David A. Resto, Peter Sang Uk Park, Thomas J. Werner, Poul F. Høilund-Carlsen, Abass Alavi
Journal: Clinical Nuclear Medicine (2022)

Abstract Uterine leiomyomas (fibroids) are common and benign hormone-dependent tumors of the uterus, often coinciding with atypical menstrual bleeding, urinary incontinence, and lower abdominal pain. The PET tracer 18 F-NaF has been used to study metastatic and benign bone disorders, but its potential use in investigating the molecular alterations of extraosseous tissues and tumors has not been fully investigated. In this report, we present a calcifying uterine leiomyoma incidentally detected on 18 F-NaF PET/CT scans in a postmenopausal 61-year-old woman and follow-up image 2 years after, highlighting the potential of 18 F-NaF in monitoring both the molecular and structural progression of uterine leiomyomas.
False-Positive for Pulmonary Emboli on Ventilation/Perfusion Scan Due to Improper Patient Positioning During Tracer Administration
Authors: Gary A. Ulaner, Catalan Grigore
Journal: Clinical Nuclear Medicine (2022)

A 67-year-old woman presented with shortness of breath and a ventilation/perfusion scan was performed. Initial images demonstrated mismatched bilateral apical defects that would be classified as high probability for pulmonary emboli. However, it was unusual that the defects were only in the bilateral apices. Investigation discovered that 99m Tc-MAA was administered while the patient was in a seated position. Repeat scan the following day with the patient in the correct, supine, position during 99m Tc-MAA administration demonstrated no defects. In this case, incorrect patient positioning could have resulted in an incorrect diagnosis of pulmonary emboli and inappropriate treatment of the patient.
Carbohydrate utilization by the gut microbiome determines host health responsiveness to whole grain type and processing methods
Authors: Caroline Smith, Mallory J. Van Haute, Yibo Xian, Rafael R. Segura Munoz, Sujun Liu, Robert J. Schmaltz, Amanda E. Ramer-Tait, Devin J. Rose
Journal: Gut Microbes (2022)

Little is known about how interactions among grain processing, grain type, and carbohydrate utilization (CU) by the microbiome influence the health benefits of whole grains. Therefore, two whole grains - brown rice and whole wheat - and two processing methods - boiling (porridge) and extrusion - were studied for their effects on host metabolic outcomes in mice harboring human microbiomes previously shown in vitro to have high or low CU. Mice carrying either microbiome experienced increases in body weight and glycemia when consuming Western diets supplemented with extruded grains versus porridge. However, mice with the high but not low CU microbiome also gained more weight and fat over time and were less glucose tolerant when consuming extruded grain diets. In high CU microbiome mice, the exacerbated negative health outcomes associated with extrusion were related to altered abundances of Lachnospiraceae and Ruminococcaceae as well as elevated sugar degradation and colonic acetate production. The amplicon sequence variants (ASVs) associated with extruded and porridge diets in this in vivo study were not the same as those identified in our prior in vitro study; however, the predicted functions were highly correlated. In conclusion, mice harboring both high and low CU microbiomes responded to the whole grain diets similarly, except the high CU microbiome mice exhibited exacerbated effects due to excessive acetate production, indicating that CU by the microbiome is linked to host metabolic health outcomes. Our work demonstrates that a greater understanding of food processing effects on the microbiome is necessary for developing foods that promote rather than diminish host health.Abbreviations: CU- carbohydrate utilization; SCFA- short-chain fatty acids; GF- germ-free; HMA, human-microbiome associated; ipGTT- intraperitoneal glucose tolerance test; HOMA-IR- Homeostatic Model Assessment for Insulin Resistance; AUC- area under the glycemia curve; ASV- amplicon sequence variant; lf- low-fat; wd- Western diet; wd_wwp- Western diet containing whole wheat porridge; wd_wwe- Western diet containing whole wheat extrudate; wd_bre- Western diet containing brown rice extrudate; wd_extr- Western diet containing either whole wheat or brown rice extrudate.
18F-FDG Muscular Uptake in Statin-Associated Symptoms Without Myositis
Authors: Gilles Metrard, Helene Besse, Aurelien Callaud, Frederique Thibault, Matthieu Bailly
Journal: Clinical Nuclear Medicine (2022)

Abstract Statin-associated muscle symptoms are a frequent adverse effect of statin treatment and can lead to a statin-associated myopathy characterized by a significant serum creatine kinase increase. We report the case of an 80-year-old man who presented an increased muscular 18 F-FDG uptake in a statin-associated muscle symptom without creatine kinase abnormality or inflammation. Statin treatment was discontinued for 6 hours, 3 days, and 7 days on consecutive follow-up examinations. The 1-week window clearly enhanced image quality. This case illustrates the possibility of diffuse muscular 18 F-FDG uptake without myositis and the need for a minimal 1-week statin discontinuation to reduce muscular uptake.
New and Persistent Sedative-Hypnotic Use After Adjuvant Chemotherapy for Breast Cancer
Authors: Jacob C Cogan, Rohit R Raghunathan, Melissa P Beauchemin, Melissa K Accordino, Yongmei Huang, Elena B Elkin, Alexander Melamed, Jason D Wright, Dawn L Hershman
Journal: JNCI Journal of the National Cancer Institute (2022)

Sedative-hypnotic medications are used to treat chemotherapy-related nausea, anxiety, and insomnia. However, prolonged sedative-hypnotic use can lead to dependence, misuse, and increased health-care use. We aimed to estimate the rates at which patients who receive adjuvant chemotherapy for breast cancer become new persistent users of sedative-hypnotic medications, specifically benzodiazepines and nonbenzodiazepine sedative-hypnotics (Z-drugs).Using the MarketScan health-care claims database, we identified sedative-hypnotic-naïve patients who received adjuvant chemotherapy for breast cancer. Patients who filled 1 and more prescriptions during chemotherapy and 2 and more prescriptions up to 1 year after chemotherapy were classified as new persistent users. Univariate and multivariable logistic regression analyses were used to estimate odds of new persistent use and associated characteristics.We identified 22 039 benzodiazepine-naïve patients and 23 816 Z-drug-naïve patients who received adjuvant chemotherapy from 2008 to 2017. Among benzodiazepine-naïve patients, 6159 (27.9%) filled 1 and more benzodiazepine prescriptions during chemotherapy, and 963 of those (15.6%) went on to become new persistent users. Among Z-drug-naïve patients, 1769 (7.4%) filled 1 and more prescriptions during chemotherapy, and 483 (27.3%) became new persistent users. In both groups, shorter durations of chemotherapy and receipt of opioid prescriptions were associated with new persistent use. Medicaid insurance was associated with new persistent benzodiazepine use (odds ratio = 1.88, 95% confidence interval = 1.43 to 2.47) compared with commercial or Medicare insurance.Patients who receive sedative-hypnotic medications during adjuvant chemotherapy for breast cancer are at risk of becoming new persistent users of these medications after chemotherapy. Providers should ensure appropriate sedative-hypnotic use through tapering dosages and encouraging nonpharmacologic strategies when appropriate.
Comparison of 68Ga-FAPI and 18F-FDG PET/CT in Finger Hidradenocarcinoma
Authors: Jie Wang, Junhao Wu, Yihui Guan, Jing Xu, Fang Xie
Journal: Clinical Nuclear Medicine (2022)

We report a case of hidradenocarcinoma, which showed only slight 18 F-FDG uptake. However, the rare sweat gland tumor demonstrated intense tracer uptake on 68 Ga-FAPI PET/CT. This case demonstrates the potential value of 68 Ga-FAPI PET/CT for the evaluation of hidradenocarcinoma.
Bilateral Axillary Nodal Uptake on 99mTc–White Blood Cell Study Secondary to COVID-19 mRNA Vaccination
Authors: Nadia A. Namous, Daniel Kushner, Simin Dadparvar
Journal: Clinical Nuclear Medicine (2022)

Abstract A 77-year-old man with a history of chronic lower back pain, and prior spinal fusion surgery X2 was referred for 99m Tc-WBC Study for evaluation of worsening back pain and cervical radiculopathy to rule out any signs of infection. The patients white blood cells were tagged with 99m Tc-HMPAO (hexamethylpropylene amine oxime), and planar and SPECT/CT imaging was performed at 4 and 24 hours. 99m Tc-WBC Study showed no abnormal isotope localization in the spine; however, there was an incidental finding of bilateral increased soft tissue uptake in axillary lymph nodes. Medical history revealed intramuscular injection of second and third dose of Moderna mRNA COVID-19 vaccine in bilateral deltoids approximately 11 and 5 months before scan.
64Cu-DOTA-Rituximab PET/CT of B-Cell Non-Hodgkin Lymphoma for Imaging the CD20 Expression
Authors: Inki Lee, Ilhan Lim, Kyo Chul Lee, Hye Jin Kang, Sang Moo Lim
Journal: Clinical Nuclear Medicine (2022)

64 Cu-DOTA-rituximab PET/CT was performed on a 62-year-old and a 71-year-old men diagnosed with B-cell non-Hodgkin lymphoma. Compared with 18 F-FDG PET/CT, lesions could be detected more sensitively, and it was confirmed that there was no discernible 64 Cu-DOTA-rituximab uptake in the tumor other than lymphoma. 64 Cu-DOTA-rituximab PET/CT could be a powerful tool for the diagnosis and monitoring treatment response of lymphoma because of imaging the CD20 expression.
NHS workers join Queen’s funeral procession
Authors: Alison Shepherd
Journal: BMJ (2022)

Advances in immunosuppressive therapy have drastically improved acute rejection rates in kidney transplant recipients over the past five decades. Nevertheless, it should remain high on any differential diagnosis of unexplained graft dysfunction because of the potential negative effect on graft longevity. Understanding the pre- and post-transplant risk factors for acute rejection can help estimate the probability of immunologic graft damage, and accurate identification of the type and severity of acute rejection will guide appropriate treatment. Tissue biopsy remains the gold standard for evaluating immunologic graft damage, and the histologic definition of acute rejection has evolved in recent years. Intravenous steroids and T cell depletion remain the standard therapy for T cell–mediated rejection and are effective in reversing most cases. Plasma exchange and intravenous Ig, with or without rituximab, are most commonly used for the treatment of antibody-mediated rejection and several newer agents have recently been investigated for severe cases. This review aims to provide the general nephrologist caring for transplant recipients with an approach to immunologic risk assessment and a summary of recent advances in the diagnosis and treatment of acute graft rejection.
Gastric dysfunction in patients with chronic nausea and vomiting syndromes defined by a noninvasive gastric mapping device
Authors: Armen A. Gharibans, Stefan Calder, Chris Varghese, Stephen Waite, Gabriel Schamberg, Charlotte Daker, Peng Du, Saeed Alighaleh, Daniel Carson, Jonathan Woodhead, Gianrico Farrugia, John A. Windsor, Christopher N. Andrews, Greg O’Grady
Journal: Science Translational Medicine (2022)

Chronic nausea and vomiting syndromes (NVSs) are prevalent and debilitating disorders. Putative mechanisms include gastric neuromuscular disease and dysregulation of brain-gut interaction, but clinical tests for objectively defining gastric motor function are lacking. A medical device enabling noninvasive body surface gastric mapping (BSGM) was developed and applied to evaluate NVS pathophysiology. BSGM was performed in 43 patients with NVS and 43 matched controls using Gastric Alimetry (Alimetry), a conformable high-resolution array (8 × 8 electrodes; 20-mm interelectrode spacing), wearable reader, and validated symptom-logging app. Continuous measurement encompassed a fasting baseline (30 minutes), 482-kilocalorie meal, and 4-hour postprandial recording, followed by spectral and spatial biomarker analyses. Meal responses were impaired in NVS, with reduced amplitudes compared to controls (median, 23.3 microvolts versus 38.0 microvolts, P &lt; 0.001), impaired fed-fasting power ratios (1.1 versus 1.6, P = 0.02), and disorganized slow waves (spatial frequency stability, 13.6 versus 49.5; P &lt; 0.001). Two distinct NVS subgroups were evident with indistinguishable symptoms (all P &gt; 0.05). Most patients (62%) had normal BSGM studies with increased psychological comorbidities (43.5% versus 7.7%; P = 0.03) and anxiety scores (median, 16.5 versus 13.0; P = 0.035). A smaller subgroup (31%) had markedly abnormal BSGM, with biomarkers correlating with symptoms (nausea, pain, excessive fullness, early satiety, and bloating; all r &gt; 0.35, P &lt; 0.05). Patients with NVS share overlapping symptoms but comprise distinct underlying phenotypes as revealed by a BSGM device. These phenotypes correlate with symptoms, which should inform clinical management and therapeutic trial design.
Covid-19 sets back progress on neglected diseases in India
Authors: Cheena Kapoor
Journal: BMJ (2022)

For 68 year old Shivji Singh, a resident of Govind Chak village in Saran district, Bihar, the past two years have meant severe financial losses and physical degradation.The head of a family of 13, Singh has lymphatic filariasis and has barely been able to work because of pain in his left leg.Also known as elephantiasis, lymphatic filariasis is caused by parasitic worms spread by mosquitoes, and is one of the leading causes of disability worldwide.Singh has lived with the condition for more than 11 years.He says access to treatment was severely curtailed during the pandemic.